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Posts Tagged ‘human variation

Genetics of High Altitude Life

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Almost every biological anthropology text-book I’ve ever looked at has described the adaptations of human populations to the environments they occupy. Examples they give are the short stalky Inuit adapted to conserving heat in cold environments, the long lanky East African nomads adapted to far distant travels, and the barrel chested Peruvian and Tibetans living in low oxygen environments.

Highland Tibet

Highland Tibet

Little discussion, beyond correlating ecology and physical observation, is given to these. Actually I lie, the physiology of the barrel chested high altitude occupants is given a couple of sentences as well as an elevated oxygen binding capacity without concentrating their blood.

A paper published in Science several days ago tackles this latter issue. A group of scientists looked for unique alleles among Tibet highlanders and discovered 10 unique oxygen-processing alleles. I don’t have full access to the publication, so can’t tell if these genes encode for completely different functioning proteins or are differentially regulated at high altitudes.

All I can derive is that these genes seem to prevent polycythemia, edematous swelling of the lungs and brain, and hypertension of the pulmonary vasculature, which are all complications of high altitude living.  Two of these genes are EGLN1 and PPARA. PPARA is a peroxisome proliferation proteins that also is a leukotriene antagonist. That is interesting because in obstructive conditions like asthama, leukotrienes induce vasospasm and bronchconstriction. EGLN1 is also has an interesting role,

“it is a protein encoded by this gene catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis.”

These two genes were significantly associated with the decreased hemoglobin phenotype that is unique to this highland population.

    Simonson TS, Yang Y, Huff CD, Yun H, Qin G, Witherspoon DJ, Bai Z, Lorenzo FR, Xing J, Jorde LB, Prchal JT, & Ge R (2010). Genetic Evidence for High-Altitude Adaptation in Tibet. Science (New York, N.Y.) PMID: 20466884

Written by Kambiz Kamrani

May 16, 2010 at 2:08 pm

Debunking Lee Berger’s Palaun Dwarf Population

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Lee Berger’s got a big problem. Rex Dalton was on his case earlier this year about Berger’s political and cultural approach to his Palaun study. And now Scott Fitzpatrick, one of the most vocal critics of Berger’s dwarves from Palau, has a new paper out in the open access journal PLoS One, where he sinks his teeth into the science behind Berger’s Palaun dwarves. His reputation as a thorough, thoughtful and careful scientist is challenged. Other authors in this paper include Greg Nelson as well as Geoffrey Clark, who specializes in island archaeology and physical anthropology — especially that of Palau.

The paper, “Small Scattered Fragments Do Not a Dwarf Make: Biological and Archaeological Data Indicate that Prehistoric Inhabitants of Palau Were Normal Sized,” argues that Berger et al. studied a fragmentary, small sample size, that other remains found from other sites in Palau fall within normal human variation, and lastly the sizes reported by Berger et al. are very similar to samples of regular humans from Chelechol ra Orrak… the latter claim was mentioned in the Elizabeth Culotta news piece, by John Hawks and Berger himself in our comment thread.

I’m not at all surprised by the points raised in this current paper. I’ve read the paper and will be reviewing it in this post. For any burgeoning physical anthropologists and paleoanthropologists out there, this is an important paper to read. The take home message of ‘don’t rush to publish and know the previous literature and samples by heart when you tread on someone else’s turf.’

In the introduction, Fitzpatrick et al.’s burst out guns a’ blazing. It is pretty much an academic slam of Berger et al.’s work. Of particular interest is Fitzpatrick et al.’s discussion about the problems with approaching comparative anatomy with a bias… Because it really gets at the heart of Berger’s issue. The authors write,

“Researchers familiar with Oceanic prehistory should work from a null hypothesis that human skeletal material found in Palau represent modern humans of normal stature and body mass… Unfortunately, it appears that Berger et al. did not do this and instead operated from a null hypothesis, based off their initial impression from a few fragments that exhibited small or primitive dimensions (one of which-apparent brow ridges—turned out to be carbonate precipitate that eventually flaked off), that their sample represented a population of small-bodied humans.”

There’s no denying that Lee Berger approached the remains with preconceived notions that he was looking at the remains of Homo floresiensis before completely assessing them. Hell, he sought out an emergency grant to study the caves thinking that he was introduced to a cash crop of Hobbits. But, that aside, there flaws can bee seen in the hard science.

Berger et al. estimated stature off of two femoral heads. John Hawks mentioned that… saying,

“Berger and colleagues have no femora sufficiently preserved to estimate length, but their two femoral heads have diameters of 38.8 and 36.1 mm.”

Hawks is right, it is hard to estimate length of a femur and ultimately height when you don’t have the whole bone. And that’s exactly what Fitzpatrick et al. address. They compare the mean values of femoral heads from Chelechol ra Orrak, a site just a few kilometers from Berger’s site. They report that while Berger et al.’s sample is smaller than the average modern human, they are only slightly less than the average diameters from Orrak. When removing the larger individual from the Orrak sample, the mean falls to ~37.16mm — meaning the maximum diameter for two individuals from Orrak is below that reported by Berger et al.

Map of Chelechol ra Orrak (blue C), Ulong (red U), Ucheliungs (green U) and Omedokel (yellow O) Cave Site in Palau

Map of Chelechol ra Orrak (blue C), Ulong (red U), Ucheliungs (green U) and Omedokel (yellow O) Cave Sites in Palau

The samples from Orrak were found in 2000 by Fitzpatrick. Orrak is just as old as Berger’s sites, around 3, 000 years before the present. The site yielded 25 individuals spanning from prenates to neonates to adolescents and adults of both sexes. There are several complete skeletons present, but only one has been excavated and the rest are a made up of a hodgepodge of elements. Here’s the catch: when looking at other measurements of the bones from Orrak, we see that they are of people of average size and stature. The Orrak females averaged about 5-foot, 1-inch in heigh, within the average accepted values of height.

Okay, what about the frontal bone? Remember the reporting of the ‘moderate bossing’ of the frontal? Well both sites reported by Berger, the Ucheliungs and Omedokel caves, are limestone rockshelters. When mixed with water, limestone as you may know deposits a hard matrix which may have caused the lumpy, primitive brow ridges on an otherwise modern human’s frontal bone. But since the frontal bone wasn’t available to Fitzpatrick et al., they take their analysis to other, quantitative measurements such the breadth of the bone.

Frontal breadth measurements taken from 14 male specimens of early Palaun populations have a range of 90 – 96 mm are most certainly small. A specimen from Orrak has a frontal measurement of 90.5mm. But the other measurements, such as the cranial length, breadth, and basion-bregma height indicate that this individual had long cranium with a normal brain size — he or she just a small face. The point to take home, as with the femoral head one, is that one measurement alone need not make a dwarf.

Berger et al. said the teeth they studied appeared megadont and therefore primitive. Megadont just means large toothed. While the teeth are undoubtedly large, they are not very primtive. Fitzpatrick et al. list four different publication which say that the ‘megadont’ measurements fall within the range of early Palaun populations of modern humans. Early Palaun populations were hunter gatherers, who did not experience a reduction in tooth morphology that came with the onset of agriculture. I’d venture to say that almost every physical anthropologist knows this. And for Berger et al. to not consider this and not review the previous literature, is just damn sloppy.

Fitzpatrick and team use the measurements from femora, crania, and teeth from Orrak to show that people from 3,000 years before the present in Palau were just simply gracile. The logical consideration is that people from same period found in the Ucheliungs and Omedokel sites are the same, not dwarves. But what about the discussion Berger et al. gave to their small-bodied ‘pygmies’ transitioning into larger-sized people around 1,000 years ago? Fitzpatrick and team go the extra mile and integrate archaeological and linguistic evidence and conclude that there aren’t any signs of external influence on Palaun language and material culture that could account for the change in larger body size.

I chuckled a bit inside when I read the conclusion in Fitzpatrick et al.’s paper. They write that they used a “sledgehammer to crack a nut,” with the wealth of evidence they showed. But you shouldn’t pity Berger. He didn’t take the time to understand the area in which he was working. That was evident with the upset he caused within Palau and the story Rex Dalton was able to extract. Greg Nelson provided the press with this scolding quote:

“Any time you work anywhere, you have to understand this history. You just can’t walk in and cowboy it, pull some stuff out and draw conclusions in the absence of understanding the bigger picture.”

    Fitzpatrick, S.M., Nelson, G.C., Clark, G., DeSalle, R. (2008). Small Scattered Fragments Do Not a Dwarf Make: Biological and Archaeological Data Indicate that Prehistoric Inhabitants of Palau Were Normal Sized. PLoS ONE, 3(8), e3015. DOI: 10.1371/journal.pone.0003015

Written by Kambiz Kamrani

August 27, 2008 at 10:30 am

Luigi Luca Cavalli-Sforza’s Interview and Pardis Sabeti in Nature

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Right on the coat tails of Jon’s post on discussing race comes an interview with Luigi Luca Cavalli-Sforza, Luigi Luca Cavalli-Sforzaa really distinguished and now emeritus population geneticist from Stanford, in Nature News. His work has been very controversial because he has consistently resisted the notion that ‘race’ has any useful biological meaning.

His work has been outlined because of the “inappropriateness of [his use of] predefined racial categories [to sort] genetic diversity.” And his ambitious proposition to start the Human Genome Diversity Project was accused of “cultural insensitivity, neocolonialism, and biopiracy.” There are a lot more criticism of him floating out there, even Bill Poser in Language Log nailed Cavalli-Sforza’s take on linguistics.

He’s been outright labeled as a racist, and in this Nature News interview he defends himself,

How did you feel about being accused of racism?
Well, many mistakes are made and that was a very curious one. I’d argued for decades that the concept of ‘race’ defined by external characteristics — such as skin colour, size variations or facial fat — is nonsense. These visible characteristics evolved under natural selection, mostly to cope with local environments, and have no deeper base.

I didn’t get angry or depressed, I only regretted how much time the objections cost to the project development.”

Similarly, Erika Check Hayden writes in Nature News on how similar we are on a base by base level, but we seem different in so many ways in phenotype. At the very end Erika drops a link to Pardis Sabeti, who is lead author of a new publication using HapMap project extensively to identify specific genes linked to human diversity.

Here’s the information of on the paper, “Genome-wide detection and characterization of positive selection in human populations,”

“With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used ‘long-range haplotype’ methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.”

Seems like a very interesting read. Hat tip to Razib.

Written by Kambiz Kamrani

October 17, 2007 at 1:42 pm

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